Linezolid-containing regimens for the treatment of drug-resistant tuberculosis in South African children

Pc, Rose; Um, Hallbauer; Seddon, James A; Ac, Hesseling; Schaaf, H. Simon

doi:10.5588/ijtld.12.0322

Cited by 48 publications

(23 citation statements)

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“…70 Five reports (three pulmonary and two meningitis) of XDR tuberculosis in children younger than 5 years with outcomes, have been published worldwide. 9–11 One patient with tuberculosis meningitis died, but the other four were either cured or had culture conversion and were continuing treatment at the time the report was published. The children were reported to have tolerated the drugs well, with PAS-induced hypothyroidism being the most common side-effect.…”

Section: Review and Discussionmentioning

confidence: 99%

“…In particular, little is known about XDR tuberculosis in young children (aged ≤5 years), with only five reports with outcomes published worldwide. 9–11 Moreover, young children are a susceptible population, with unique difficulties associated with the management of tuberculosis. Diagnosis is challenging because of the paucibacillary nature of infection and difficulties in obtaining appropriate clinical specimens, leading to diagnostic uncertainties and delays.…”

Section: Introductionmentioning

confidence: 99%

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Extensively drug-resistant tuberculosis in a young child after travel to India

Salazar-Austin

Ordoñez

Hsu

et al. 2015

The Lancet Infectious Diseases

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Extensively drug-resistant (XDR) tuberculosis is becoming increasingly prevalent worldwide, but little is known about XDR tuberculosis in young children. In this Grand Round we describe a 2-year-old child from the USA who developed pneumonia after a 3 month visit to India. Symptoms resolved with empirical first-line tuberculosis treatment; however, a XDR strain of Mycobacterium tuberculosis grew in culture. In the absence of clinical or microbiological markers, low-radiation exposure pulmonary CT imaging was used to monitor treatment response, and guide an individualised drug regimen. Management was complicated by delays in diagnosis, uncertainties about drug selection, and a scarcity of child-friendly formulations. Treatment has been successful so far, and the child is in remission. This report of XDR tuberculosis in a young child in the USA highlights the risks of acquiring drug-resistant tuberculosis overseas, and the unique challenges in management of tuberculosis in this susceptible population.

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Section: Review and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Extensively drug-resistant tuberculosis in a young child after travel to India

Salazar-Austin

Ordoñez

Hsu

et al. 2015

The Lancet Infectious Diseases

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“…These included prospective and retrospective observational studies. Figure 1 shows how a cohort of fluoroquinoloneresistant MDR-TB patients treated with WHO group 5 drugs was assembled from 20 articles (6,(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). The cohort consisted of 194 patients from 12 countries: 117 from four Asian regions (South Korea, China, Hong Kong, and India), 40 from five European countries (Portugal, Italy, Germany, Belgium, and Spain), 36 from two North and South American countries (the United States and Argentina), and 1 from South Africa.…”

Section: Findings and Conclusionmentioning

confidence: 99%

WHO Group 5 Drugs and Difficult Multidrug-Resistant Tuberculosis: a Systematic Review with Cohort Analysis and Meta-Analysis

Chang¹,

Yew

Tam³

et al. 2013

Antimicrob Agents Chemother

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It is often necessary to include WHO group 5 drugs in the treatment of extensively drug-resistant tuberculosis (XDR-TB) and fluoroquinolone-resistant multidrug-resistant tuberculosis (MDR-TB). As clinical evidence about the use of group 5 drugs is scarce, we conducted a systematic review using published individual patient data. We searched PubMed and OvidSP through 7 April 2013 for publications in English to assemble a cohort with fluoroquinolone-resistant MDR-TB treated with group 5 drugs. Favorable outcome was defined as sputum culture conversion, cure, or treatment completion in the absence of death, default, treatment failure, or relapse. A cohort of 194 patients was assembled from 20 articles involving 12 geographical regions. In descending order of frequency, linezolid was used in treatment of 162 (84%) patients, macrolides in 84 (43%), clofazimine in 65 (34%), amoxicillin with clavulanate in 56 (29%), thioridazine in 18 (9%), carbapenem in 16 (8%), and high-dose isoniazid in 16 (8%). Cohort analysis with robust Poisson regression models and random-effects meta-analysis similarly suggested that linezolid use significantly increased the probability (95% confidence interval) of favorable outcome by 57% (10% to 124%) and 55% (10% to 121%), respectively. Defining significant associations by risk ratios > 1.2 or < 0.9, neither cohort analysis nor meta-analysis demonstrated any significant add-on benefit from the use of other group 5 drugs with respect to outcome for patients treated with linezolid, although selection bias might have led to underestimation of their effects. Our findings substantiated the use of linezolid in the treatment of XDR-TB or fluoroquinolone-resistant MDR-TB and call for further studies to evaluate the roles of other group 5 drugs.

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“…Lactic acidosis occurs across a broad age range and has been described in children as well (8). Pancreatitis has also been reported as a complication of linezolid therapy, but appears to be isolated to the pediatric population (9,10).…”

Section: Discussionmentioning

confidence: 99%